This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During the past year, we solved the problem of reduced success experienced during the previous report period. After resolving a number of technical problems involving the isolation and processing of the neonatal porcine islets, and a new nonhuman primate diabetes induction method by streptozocin, we have been able to reproduce our original success of transplanting porcine islets into recipient diabetic macaques with sustained resolution of hyperglycemia and survival of porcine islets for 180 days under cover of a costimulation blockade-based immunosuppression regimen. Guided by success in our alloislet nonhuman primate model, more favorable and clinically relevant treatment protocols were applied to our xenoislet model with very promising results. Once optimized, the new drug regimen will be used to determine the optimal islet mass and implantation site, establishing a foundation for moving porcine islet transplantation into clinical trials.